1. Field of the Invention
The present invention is generally directed to liquid solvent handling systems and, more particularly, an improved solvent pressurization distribution and sparging system for use with a high pressure liquid chromatograph.
2. Discussion of the Related Art
In recent years, high pressure liquid chromatography (HPLC) has become an increasingly important analytical tool. The systems have become increasingly sophisticated; today, an unattended analysis may involve analyzing multiple portions of a sample utilizing a variety of different solvents or analyzing a variety of samples with the same or different solvents. Such a system requires a sophisticated solvent distribution system. The solvent distribution system must be capable of the automatic metering of precise amounts of solvents and have the ability to switch from one solvent composition to another on an automated basis. Such solvent systems include a plurality of solvent containers connected by a manifold with a source of sparging gas, normally helium, which is used to remove dissolved gases from the solvent prior to use with the chromatograph and to pressurize the system. Each solvent container is also provided with an output conduit or tube which connects it with the solvent input access of the liquid chromatograph device. These systems are normally operated under positive pressure such that the solvent is forced rather than drawn out of the solvent container into the chromatograph device.
Manifolding multiple solvent containers together has enabled progress to be made in the automation of processing multiple tests on the chromatograph. It has, however, generated some important, heretofore unsolved, liquid handling problems.
Solvent handling systems of the class described now in use are typified by systems such as that illustrated in U.S. Pat. No. 4,448,684 issued May 15, 1984 to Paradis which describes a solvent pressurization system which includes delivery and sparging modes together with a venting system. One problem associated with such prior art manifolded, pressurized solvent distribution systems involves cross-contamination or the inadvertent mixing of solvents. Because the several solvent containers are manifolded together in parallel with respect to receiving sparging gas, such as helium from a common source, the contents of all of the containers have access to at least one common point. At certain times imbalances in the pressure between containers are likely to occur within the system. This produces a tendency for solvents from one or more containers to be forced or drawn up through the manifold and into one or more of the other containers under given circumstances. This may occur, for example, when a bottle or a particular solvent container is opened for refilling without the system first being depressurized. When this happens, solvent flows from a pressurized bottle to the unpressurized one by way of the manifold thus contaminating the entire distribution system.
In a related problem, the relatively high diffusion rate associated with the relatively small helium molecules reduces the supply pressure in the distribution lines and may actually cause negative pressures to occur in certain of the distribution lines when the pressure is removed from the system. The result is a lower pressure in the line than in the connected solvent vessel. This causes back flow of solvent from one or more of the containers into the manifold also resulting in complete cross contamination of the system.
High pressure liquid chromatography systems have traditionally utilized instrumentation designed for the chemical laboratory without reference to biocompatibility. Thus, for example, the materials used in such systems, while being relatively corrosion resistant, generally, have not been suitable for use with the types of highly corrosive mobile phases typically used in biological separations. Typical mobile phases for biological separations contain concentrations of salts, acids or bases which are proven to erode stainless steel, attack seals and provide a breeding ground for microorganisms. Because they are operated under pressure, normally these systems are housed within safety enclosures to minimize damage from any solvent which might leak from one or more of the several vessels.
Instrumentation manufacturers, then, also have to address the problem of making such systems biologically compatible or inert. In addition, systems must be able to withstand the pressure and meet other physical requirements such as minimizing leakage or loss of sparging gas through container tops and vents.
Accordingly, there exists a need to construct a biocompatible solvent handling and distribution system in which cross contamination problems are eliminated. The need exists for the materials of construction to exhibit biocompatibility and for container accesses and vents to be gas-tight when closed.